Knee osteoarthritis (OA) is a leading cause of chronic disability in older persons. The course of knee OA is variable. A widely-accepted paradigm views knee OA severity as the result of local neuromuscular and mechanical factors, acting against a background of susceptibility-determining systemic factors. The local factors include structural elements and joint-protective neuromuscular activity. Impairments in these factors result in increased, suboptimally distributed load transmitted to the articular surface, and may be associated with accelerated disease progression. In this study, we test the hypothesis that malalignment, increased laxity, proprioception deficit, and muscle weakness are associated with more rapid progression of knee OA. Our specific aims are: 1) to measure in 300 patients with tibiofemoral knee OA, defined by radiographic criteria, at baseline, 18 months and 36 months, each of the neuromuscular and mechanical factors noted; 2) to assess change in outcomes, i.e. functional status, using the Western Ontario and McMaster University OA Index Physical Function scale, and radiographic status by measuring joint space width on weight bearing, semi-flexed, fluoro- confirmed knee radiographs; and 3) to analyze the contribution of each of the local factors to outcome, while controlling for potentially confounding variables, using analytic methods that allow data from both knees to be considered. The results of this natural history study will aid the delineation of the specific events that cause progression of knee OA, suggest targets for non-surgical and surgical intervention development, aid correct interpretation of therapeutic trial results, and facilitate early, cost-effective intervention in mechanical subsets at particular risk for decline.